Lack of means to consistently meet basic material needs results in poor health, particularly for those already managing chronic conditions such as HIV or cardiovascular disease (CVD). Although addressing material needs insecurities likely can be cost-effective by preventing acquisition of or exacerbation of chronic diseases, little is known about how these material needs work together to harm health. We propose to use an intersectional perspective and examine the combined effects of four different types of insecurity related to basic material needs (food, housing, financial, and healthcare) on HIV and CVD outcomes among both men and women. Material- need insecurities include absolute insufficiency of resources (hunger, homelessness, inadequate finances, no health insurance), poor quality of resources ((e.g., poor diets, healthcare coverage), uncertainty of consistently meeting future needs, and having to engage in socially unacceptable means to meet needs. An intersectional perspective allows us to examine how different combinations of these insecurities affect health in a non-additive way and may lead to more effective interventions that target co-occurring needs simultaneously, rather than investing in narrowly focused piecemeal solutions. Specifically, we aim to determine: 1) the separate and intersectional effects of four specific material-need insecurities (food, housing, financial, and healthcare insecurity) on HIV and cardiovascular outcomes using latent profile and latent transition analyses; 2) the intermediate outcomes that may be on causal paths between material-need insecurities and HIV and CVD risk outcomes using a convergent parallel mixed method design; and 3) factors that moderate effects of material- need insecurities on HIV and cardiovascular outcomes using convergent parallel mixed methods. We hypothesize that: 1) intersectional effects will more accurately identify individuals at risk for worse outcomes compared to independent effects for both HIV-infected and uninfected individuals; 2) relationships of material- need insecurities with HIV and cardiovascular outcomes are mediated by health behavior (medication non- adherence, low physical activity, missed clinic visits), mental health (stress, depression, poverty-related stigma), and physiologic (poor nutrition, inflammation) paths; and 3) inter- and intra-personal resources (e.g., social support, resilience) mitigate impacts of material-need insecurities. To address these aims, we will leverage the extensive physical exam, laboratory and survey data from the MACS and WIHS Combined Cohort Study (MWCCS), and add survey measures and blood collection in a longitudinal five-year study among over 3000 HIV-infected and at-risk MWCCS participants. We will also conduct a longitudinal qualitative study (N = 42) in three MWCCS sites. Integrating findings from this mixed-methods research will facilitate a deeper understanding of the experience, distribution, intersections, health implications, and mitigating factors of multiple material-need insecurities experienced by people living with or at-risk for HIV in the US. Subsequently, we plan to develop tailored, multi-modal interventions which can target at-risk populations and associated mechanisms.